1. Field of the Invention
This invention relates to anti-inflammatory and analgesic compounds, especially to certain quinoline derivatives, pharmaceutical compositions containing them, methods for their use, and methods for preparing these compounds.
Non-steroidal, antiinflammatory drugs (NSAIDs), have a problem of causing serious side-effects such as gastrointestinal tract or nephro-toxicity. NSAIDs inhibit the activity of cyclooxygenase (COX), which is an enzyme involved in prostaglandin G/H synthesis, resulting in the inhibition of the biosynthesis of prostaglandins not only in inflammatory loci but also in stomach and kidney. It has been found that COX exists in two forms: COX-1 and COX-2, Cell, 83, 345, (1995).
COX-1 is expresed in normal cells and controls the function of stomach and kidney, while COX-2 is induced by mitogens or cytokines in inflammatory sites where inflammation and other immunoreactions occur, J. Biol. Chem., 271, 33157(1996).
To avoid the toxicity of NSAIDs due to the inhibition of coexisting COX-1, selective inhibitors of COX-2 have been investigated. The selective COX-2 inhibitors have antiinflammatory action, pain-relieving action, and/or antipyretic action; with less side effects, such as bleeding in the gastrointestinal tract, COX-2 inhibitors may show anticancer activity, and lower the induction of asthma in asthmatic patients who are sensitive to conventional NSAIDs. These selective inhibitors of COX-2 may also be used in treating Alzheimer's disease and osteoporosis of women after menopause.
2. Description of Related Art    U.S. Pat. No. 6,077,850 (G. D. Searle) discloses 1,2-dihydroquinoline derivatives for use in treating cyclooxygenase-2 mediated disorders.    U.S. Pat. No. 6,069,151 (Darwin Discovery, Ltd.) discloses quinolines and their therapeutic usee.    U.S. Pat. No. 5,962,531 (Syntex USA, Inc) discloses 5-aroylnaphthalene derivatives as anti-inflammatory agents.    U.S. Pat. No. 5,221,677 (Imperial Chemical Industries PLC) discloses quinoline or isoquinoline derivatives as 5-lipoxygenase inhibitors.